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Early diagnosis interventions such as symptom awareness campaigns increasingly form part of global cancer control strategies. However, these strategies will have little impact in improving cancer outcomes if the targeted symptoms represent advanced stage of disease. Therefore, we aimed to examine associations between common presenting symptoms of cancer and stage at diagnosis. In this cross-sectional study, we analysed population-level data from the English National Cancer Diagnosis Audit 2014 for patients aged 25 years and older with one of 12 types of solid tumours (bladder, breast, colon, endometrial, laryngeal, lung, melanoma, oral or oropharyngeal, ovarian, prostate, rectal, and renal cancer). We considered 20 common presenting symptoms and examined their associations with stage at diagnosis (TNM stage IV vs stage I–III) using logistic regression. For each symptom, we estimated these associations when reported as a single presenting symptom and when reported together with other symptoms. We analysed data for 7997 patients. The proportion of patients diagnosed with stage IV cancer varied substantially by presenting symptom, from 1% (95% CI 1–3; eight of 584 patients) for abnormal mole to 80% (71–87; 84 of 105 patients) for neck lump. Three of the examined symptoms (neck lump, chest pain, and back pain) were consistently associated with increased odds of stage IV cancer, whether reported alone or with other symptoms, whereas the opposite was true for abnormal mole, breast lump, postmenopausal bleeding, and rectal bleeding. For 13 of the 20 symptoms (abnormal mole, breast lump, post-menopausal bleeding, rectal bleeding, lower urinary tract symptoms, haematuria, change in bowel habit, hoarseness, fatigue, abdominal pain, lower abdominal pain, weight loss, and the “any other symptom” category), more than 50% of patients were diagnosed at stages other than stage IV; for 19 of the 20 studied symptoms (all except for neck lump), more than a third of patients were diagnosed at stages other than stage IV. Despite specific presenting symptoms being more strongly associated with advanced stage at diagnosis than others, for most symptoms, large proportions of patients are diagnosed at stages other than stage IV. These findings provide support for early diagnosis interventions targeting common cancer symptoms, countering concerns that they might be simply expediting the detection of advanced stage disease. UK Department of Health's Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis; and Cancer Research UK.

During the COVID-19 lockdown, referrals via the 2-week-wait urgent pathway for suspected cancer in England, UK, are reported to have decreased by up to 84%. We aimed to examine the impact of different scenarios of lockdown-accumulated backlog in cancer referrals on cancer survival, and the impact on survival per referred patient due to delayed referral versus risk of death from nosocomial infection with severe acute respiratory syndrome coronavirus 2. In this modelling study, we used age-stratified and stage-stratified 10-year cancer survival estimates for patients in England, UK, for 20 common tumour types diagnosed in 2008–17 at age 30 years and older from Public Health England. We also used data for cancer diagnoses made via the 2-week-wait referral pathway in 2013–16 from the Cancer Waiting Times system from NHS Digital. We applied per-day hazard ratios (HRs) for cancer progression that we generated from observational studies of delay to treatment. We quantified the annual numbers of cancers at stage I–III diagnosed via the 2-week-wait pathway using 2-week-wait age-specific and stage-specific breakdowns. From these numbers, we estimated the aggregate number of lives and life-years lost in England for per-patient delays of 1–6 months in presentation, diagnosis, or cancer treatment, or a combination of these. We assessed three scenarios of a 3-month period of lockdown during which 25%, 50%, and 75% of the normal monthly volumes of symptomatic patients delayed their presentation until after lockdown. Using referral-to-diagnosis conversion rates and COVID-19 case-fatality rates, we also estimated the survival increment per patient referred. Across England in 2013–16, an average of 6281 patients with stage I–III cancer were diagnosed via the 2-week-wait pathway per month, of whom 1691 (27%) would be predicted to die within 10 years from their disease. Delays in presentation via the 2-week-wait pathway over a 3-month lockdown period (with an average presentational delay of 2 months per patient) would result in 181 additional lives and 3316 life-years lost as a result of a backlog of referrals of 25%, 361 additional lives and 6632 life-years lost for a 50% backlog of referrals, and 542 additional lives and 9948 life-years lost for a 75% backlog in referrals. Compared with all diagnostics for the backlog being done in month 1 after lockdown, additional capacity across months 1–3 would result in 90 additional lives and 1662 live-years lost due to diagnostic delays for the 25% backlog scenario, 183 additional lives and 3362 life-years lost under the 50% backlog scenario, and 276 additional lives and 5075 life-years lost under the 75% backlog scenario. However, a delay in additional diagnostic capacity with provision spread across months 3–8 after lockdown would result in 401 additional lives and 7332 life-years lost due to diagnostic delays under the 25% backlog scenario, 811 additional lives and 14 873 life-years lost under the 50% backlog scenario, and 1231 additional lives and 22 635 life-years lost under the 75% backlog scenario. A 2-month delay in 2-week-wait investigatory referrals results in an estimated loss of between 0·0 and 0·7 life-years per referred patient, depending on age and tumour type. Prompt provision of additional capacity to address the backlog of diagnostics will minimise deaths as a result of diagnostic delays that could add to those predicted due to expected presentational delays. Prioritisation of patient groups for whom delay would result in most life-years lost warrants consideration as an option for mitigating the aggregate burden of mortality in patients with cancer. None.

Summary Evidence arising from primary care electronic health records can help to assess the risk of symptomatic-but-as-yet-undiagnosed cancer. Existing evidence and methodological innovations in this field of study hold further promise for improving the diagnostic process and achieving earlier diagnosis in cancer patients.

BackgroundThe management of adults presenting with fatigue presents a diagnostic challenge, particularly regarding possible underlying cancer.MethodsUsing electronic health records, we examined cancer risk in patients presenting to primary care with new-onset fatigue in England during 2007–2013, compared to general population estimates. We examined variation by age, sex, deprivation, and time following presentation.FindingsOf 250,606 patients presenting with fatigue, 12-month cancer risk exceeded 3% in men aged 65 and over and women aged 80 and over, and 6% in men aged 80 and over. Nearly half (47%) of cancers were diagnosed within 3 months from first fatigue presentation. Site-specific cancer risk was higher than the general population for most cancers studied, with greatest relative increases for leukaemia, pancreatic and brain cancers.ConclusionsIn older patients, new-onset fatigue is associated with cancer risk exceeding current thresholds for urgent specialist referral. Future research should consider how risk is modified by the presence or absence of other signs and symptoms. Excess cancer risk wanes rapidly after 3 months, which could inform the duration of a ‘safety-netting’ period. Fatigue presentation is not strongly predictive of any single cancer, although certain cancers are over-represented; this knowledge can help prioritise diagnostic strategies.

Identifying patients presenting with nonspecific abdominal symptoms who have underlying cancer is a challenge. Common blood tests are widely used to investigate these symptoms in primary care, but their predictive value for detecting cancer in this context is unknown. We quantify the predictive value of 19 abnormal blood test results for detecting underlying cancer in patients presenting with 2 nonspecific abdominal symptoms. Using data from the UK Clinical Practice Research Datalink (CPRD) linked to the National Cancer Registry, Hospital Episode Statistics and Index of Multiple Deprivation, we conducted a population-based cohort study of patients aged ≥30 presenting to English general practice with abdominal pain or bloating between January 2007 and October 2016. Positive and negative predictive values (PPV and NPV), sensitivity, and specificity for cancer diagnosis (overall and by cancer site) were calculated for 19 abnormal blood test results co-occurring in primary care within 3 months of abdominal pain or bloating presentations. A total of 9,427/425,549 (2.2%) patients with abdominal pain and 1,148/52,321 (2.2%) with abdominal bloating were diagnosed with cancer within 12 months post-presentation. For both symptoms, in both males and females aged ≥60, the PPV for cancer exceeded the 3% risk threshold used by the UK National Institute for Health and Care Excellence for recommending urgent specialist cancer referral. Concurrent blood tests were performed in two thirds of all patients (64% with abdominal pain and 70% with bloating). In patients aged 30 to 59, several blood abnormalities updated a patient's cancer risk to above the 3% threshold: For example, in females aged 50 to 59 with abdominal bloating, pre-blood test cancer risk of 1.6% increased to: 10% with raised ferritin, 9% with low albumin, 8% with raised platelets, 6% with raised inflammatory markers, and 4% with anaemia. Compared to risk assessment solely based on presenting symptom, age and sex, for every 1,000 patients with abdominal bloating, assessment incorporating information from blood test results would result in 63 additional urgent suspected cancer referrals and would identify 3 extra cancer patients through this route (a 16% relative increase in cancer diagnosis yield). Study limitations include reliance on completeness of coding of symptoms in primary care records and possible variation in PPVs if extrapolated to healthcare settings with higher or lower rates of blood test use. In patients consulting with nonspecific abdominal symptoms, the assessment of cancer risk based on symptoms, age and sex alone can be substantially enhanced by considering additional information from common blood test results. Male and female patients aged ≥60 presenting to primary care with abdominal pain or bloating warrant consideration for urgent cancer referral or investigation. Further cancer assessment should also be considered in patients aged 30 to 59 with concurrent blood test abnormalities. This approach can detect additional patients with underlying cancer through expedited referral routes and can guide decisions on specialist referrals and investigation strategies for different cancer sites.

Key Points The diagnosis of cancer as an emergency is associated with a substantially worse prognosis; however, this represents an understudied problem, with evidence examining its frequency and aetiology limited to a few developed countries Most available evidence defines diagnosis of cancer as an emergency contextually instead of employing clinical criteria regarding presentation severity, and uses administrative data as opposed to reviews of medical records An emergency diagnosis of cancer often has a complex aetiology, involving tumour, patient and health-care related factors; evidence on the role of tumour and health-care related factors is particularly sparse Studying variations in the risk of emergency presentations by prior health-care use and related symptoms can elucidate how some emergency presentations could potentially be prevented Sociodemographic inequalities in the risks of emergency presentation underline the contribution of psychosocial factors and the potential for targeting of public health campaigns regarding cancer symptoms Optimising screening can help to reduce emergency presentations of patients with colorectal cancer Patients diagnosed with cancer through an emergency presentation have worse outcomes compared with those in whom cancer is diagnosed through other routes; therefore, reducing the number of patients presenting as an emergency with cancer will improve patients' outcomes. In this Review, the authors describe the available evidence in this area, and provide recommendations for future research, clinical practice and public health policy. Many patients with cancer are diagnosed through an emergency presentation, which is associated with inferior clinical and patient-reported outcomes compared with those of patients who are diagnosed electively or through screening. Reducing the proportion of patients with cancer who are diagnosed as emergencies is, therefore, desirable; however, the optimal means of achieving this aim are uncertain owing to the involvement of different tumour, patient and health-care factors, often in combination. Most relevant evidence relates to patients with colorectal or lung cancer in a few economically developed countries, and defines emergency presentations contextually (that is, whether patients presented to emergency health-care services and/or received emergency treatment shortly before their diagnosis) as opposed to clinically (whether patients presented with life-threatening manifestations of their cancer). Consistent inequalities in the risk of emergency presentations by patient characteristics and cancer type have been described, but limited evidence is available on whether, and how, such presentations can be prevented. Evidence on patients' symptoms and health-care use before presentation as an emergency is sparse. In this Review, we describe the extent, causes and implications of a diagnosis of cancer following an emergency presentation, and provide recommendations for public health and health-care interventions, and research efforts aimed at addressing this under-researched aspect of cancer diagnosis.

BackgroundCancer patients often have pre-existing comorbidities, which can influence timeliness of cancer diagnosis. We examined symptoms, investigations and emergency presentation (EP) risk among colorectal cancer (CRC) patients by comorbidity status.MethodsUsing linked cancer registration, primary care and hospital records of 4836 CRC patients (2011–2015), and multivariate quantile and logistic regression, we examined variations in specialist investigations, diagnostic intervals and EP risk.ResultsAmong colon cancer patients, 46% had at least one pre-existing hospital-recorded comorbidity, most frequently cardiovascular disease (CVD, 18%). Comorbid versus non-comorbid cancer patients more frequently had records of anaemia (43% vs 38%), less frequently rectal bleeding/change in bowel habit (20% vs 27%), and longer intervals from symptom-to-first relevant test (median 136 vs 74 days). Comorbid patients were less likely investigated with colonoscopy/sigmoidoscopy, independently of symptoms (adjusted OR = 0.7[0.6, 0.9] for Charlson comorbidity score 1–2 and OR = 0.5 [0.4–0.7] for score 3+ versus 0. EP risk increased with comorbidity score 0, 1, 2, 3+: 23%, 35%, 33%, 47%; adjusted OR = 1.8 [1.4, 2.2]; 1.7 [1.3, 2.3]; 3.0 [2.3, 4.0]) and for patients with CVD (adjusted OR = 2.0 [1.5, 2.5]).ConclusionsComorbid individuals with as-yet-undiagnosed CRC often present with general rather than localising symptoms and are less likely promptly investigated with colonoscopy/sigmoidoscopy. Comorbidity is a risk factor for diagnostic delay and has potential, additionally to symptoms, as risk-stratifier for prioritising patients needing prompt assessment to reduce EP.

Objective Younger people, minority ethnic groups, sexual minorities and people of lower socioeconomic status report poorer experiences of primary care. In light of NHS ambitions to reduce unwarranted variations in care, we aimed to investigate whether inequalities in patient experience of primary care changed between 2011 and 2017, using data from the General Practice Patient Survey in England. Methods We considered inequalities in relation to age, sex, deprivation, ethnicity, sexual orientation and geographical region across five dimensions of patient experience: overall experience, doctor communication, nurse communication, access and continuity of care. We used linear regression to explore whether the magnitude of inequalities changed between 2011 and 2017, using mixed models to assess changes within practices and models without accounting for practice to assess national trends. Results We included 5,241,408 responses over 11 survey waves from 2011–2017. There was evidence that inequalities changed over time (p < 0.05 for 27/30 models), but the direction and magnitude of changes varied. Changes in gaps in experience ranged from a 1.6 percentage point increase for experience of access among sexual minorities, to a 5.6 percentage point decrease for continuity, where experience worsened for older ages. Inequalities in access in relation to socio-economic status remained reasonably stable for individuals attending the same GP practice; nationally inequalities in access increased 2.1 percentage points (p < 0.0001) between respondents living in more/less deprived areas, suggesting access is declining fastest in practices in more deprived areas. Conclusions There have been few substantial changes in inequalities in patient experience of primary care between 2011 and 2017.

The nature of cancer control is changing, with an increasing emphasis, fuelled by public and political demand, on prevention, early diagnosis, and patient experience during and after treatment. At the same time, primary care is increasingly promoted, by governments and health funders worldwide, as the preferred setting for most health care for reasons of increasing need, to stabilise health-care costs, and to accommodate patient preference for care close to home. It is timely, then, to consider how this expanding role for primary care can work for cancer control, which has long been dominated by highly technical interventions centred on treatment, and in which the contribution of primary care has been largely perceived as marginal. In this Commission, expert opinion from primary care and public health professionals with academic and clinical cancer expertise—from epidemiologists, psychologists, policy makers, and cancer specialists—has contributed to a detailed consideration of the evidence for cancer control provided in primary care and community care settings. Ranging from primary prevention to end-of-life care, the scope for new models of care is explored, and the actions needed to effect change are outlined. The strengths of primary care—its continuous, coordinated, and comprehensive care for individuals and families—are particularly evident in prevention and diagnosis, in shared follow-up and survivorship care, and in end-of-life care. A strong theme of integration of care runs throughout, and its elements (clinical, vertical, and functional) and the tools needed for integrated working are described in detail. All of this change, as it evolves, will need to be underpinned by new research and by continuing and shared multiprofessional development.

Information from patient surveys can help to identify patient groups and cancers with the greatest potential for improvement in the experience and timeliness of cancer diagnosis. We aimed to examine variation in the number of pre-referral consultations with a general practitioner between patients with different cancers and sociodemographic characteristics. We analysed data from 41 299 patients with 24 different cancers who took part in the 2010 National Cancer Patient Experience Survey in England. We examined variation in the number of general practitioner consultations with cancer symptoms before hospital referral to diagnose cancer. Logistic regression was used to identify independent predictors of three or more pre-referral consultations, adjusting for cancer type, age, sex, deprivation quintile, and ethnic group. We identified wide variation between cancer types in the proportion of patients who had visited their general practitioner three or more times before hospital referral (7·4% [625 of 8408] for breast cancer and 10·1% [113 of 1124] for melanoma; 41·3% [193 of 467] for pancreatic cancer and 50·6% [939 of 1854] for multiple myeloma). In multivariable analysis, with patients with rectal cancer as the reference group, those with subsequent diagnosis of multiple myeloma (odds ratio [OR] 3·42, 95% CI 3·01–3·90), pancreatic cancer (2·35, 1·91–2·88), stomach cancer (1·96, 1·65–2·34), and lung cancer (1·68, 1·48–1·90) were more likely to have had three or more pre-referral consultations; conversely patients with subsequent diagnosis of breast cancer (0·19; 0·17–0·22), melanoma (0·34, 0·27–0·43), testicular cancer (0·47, 0·33–0·67), and endometrial cancer (0·59, 0·49–0·71) were more likely to have been referred to hospital after only one or two consultations. The probability of three or more pre-referral consultations was greater in young patients (OR for patients aged 16–24 years vs 65–74 years 2·12, 95% CI 1·63–2·75; p<0·0001), those from ethnic minorities (OR for Asian vs white 1·73, 1·45–2·08; p<0·0001; OR for black vs white 1·83, 1·51–2·23; p<0·0001), and women (OR for women vs men 1·28, 1·21–1·36; p<0·0001). We identified strong evidence of interactions between cancer type and age group and sex (p<0·0001 for both), and between age and ethnicity (p=0·0013). The model including these interactions showed a particularly strong sex effect for bladder cancer (OR for women vs men 2·31, 95% CI 1·98–2·69) and no apparent ethnic group differences in young patients aged 16–24 years, whilst the only cancers without an apparent age gradient were testicular cancer and mesothelioma. Our findings could help to prioritise and stratify early diagnosis initiatives and research, focusing on patients with cancers and sociodemographic characteristics with the largest potential for improvement. None.